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Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells.

Xu Y, Watanabe T, Tanigawa T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T - J Clin Biochem Nutr (2009)

Bottom Line: The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively.GW4064 also induced expression of these molecules.The effects of CDCA and GW4064 on expression of Cdx2 and MUC2 were abolished by guggulsterone.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.

ABSTRACT
Clinical and experimental studies showed that the reflux of bile into the stomach contributes to the induction of intestinal metaplasia of the stomach and gastric carcinogenesis. Caudal-type homeobox 2 (Cdx2) plays a key role in the exhibition of intestinal phenotypes by regulating the expression of intestine-specific genes such as goblet-specific gene mucin 2 (MUC2). We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (CDCA)-induced expression of Cdx2 and MUC2 in normal rat gastric epithelial cells (RGM-1 cells). RGM-1 cells were treated with CDCA or GW4064, an FXR agonist, in the presence or absence of guggulsterone, an FXR antagonist. CDCA induced dose-dependent expression of Cdx2 and MUC2 at both the mRNA and protein levels. The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively. GW4064 also induced expression of these molecules. The effects of CDCA and GW4064 on expression of Cdx2 and MUC2 were abolished by guggulsterone. These findings suggest that bile acids may induce gastric intestinal metaplasia and carcinogenesis through the FXR.

No MeSH data available.


Related in: MedlinePlus

Expression of the FXR in RGM-1 cells. The expression of the FXR was assessed by immunofluorescence.
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Figure 4: Expression of the FXR in RGM-1 cells. The expression of the FXR was assessed by immunofluorescence.

Mentions: During normal physiological conditions, the expression of the FXR is generally thought to be limited to the liver, intestine, kidney and adrenal glands [21, 22]. Zhang et al., [23] however, reported that the FXR is also expressed in the stomach. But because there are few reports documenting the expression of the FXR in the stomach, we investigated whether RGM-1 cells expressed the FXR. As shown in Fig. 4, immunofluorescence staining clearly demonstrated the nuclear localization of the FXR in these cells.


Bile acids induce cdx2 expression through the farnesoid x receptor in gastric epithelial cells.

Xu Y, Watanabe T, Tanigawa T, Machida H, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T - J Clin Biochem Nutr (2009)

Expression of the FXR in RGM-1 cells. The expression of the FXR was assessed by immunofluorescence.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2803137&req=5

Figure 4: Expression of the FXR in RGM-1 cells. The expression of the FXR was assessed by immunofluorescence.
Mentions: During normal physiological conditions, the expression of the FXR is generally thought to be limited to the liver, intestine, kidney and adrenal glands [21, 22]. Zhang et al., [23] however, reported that the FXR is also expressed in the stomach. But because there are few reports documenting the expression of the FXR in the stomach, we investigated whether RGM-1 cells expressed the FXR. As shown in Fig. 4, immunofluorescence staining clearly demonstrated the nuclear localization of the FXR in these cells.

Bottom Line: The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively.GW4064 also induced expression of these molecules.The effects of CDCA and GW4064 on expression of Cdx2 and MUC2 were abolished by guggulsterone.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.

ABSTRACT
Clinical and experimental studies showed that the reflux of bile into the stomach contributes to the induction of intestinal metaplasia of the stomach and gastric carcinogenesis. Caudal-type homeobox 2 (Cdx2) plays a key role in the exhibition of intestinal phenotypes by regulating the expression of intestine-specific genes such as goblet-specific gene mucin 2 (MUC2). We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (CDCA)-induced expression of Cdx2 and MUC2 in normal rat gastric epithelial cells (RGM-1 cells). RGM-1 cells were treated with CDCA or GW4064, an FXR agonist, in the presence or absence of guggulsterone, an FXR antagonist. CDCA induced dose-dependent expression of Cdx2 and MUC2 at both the mRNA and protein levels. The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively. GW4064 also induced expression of these molecules. The effects of CDCA and GW4064 on expression of Cdx2 and MUC2 were abolished by guggulsterone. These findings suggest that bile acids may induce gastric intestinal metaplasia and carcinogenesis through the FXR.

No MeSH data available.


Related in: MedlinePlus